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dc.contributor.authorHnisz, Denes
dc.contributor.authorLi, Zhaodong
dc.contributor.authorWeichert-Leahey, Nina
dc.contributor.authorRahman, Sunniyat
dc.contributor.authorLiu, Yu
dc.contributor.authorEtchin, Julia
dc.contributor.authorLi, Benshang
dc.contributor.authorShen, Shuhong
dc.contributor.authorZhang, Jinghui
dc.contributor.authorLook, A. Thomas
dc.contributor.authorMansour, Marc R.
dc.contributor.authorAbraham, Brian Joseph
dc.contributor.authorWeintraub, Abraham Selby
dc.contributor.authorKwiatkowski, Nick
dc.contributor.authorLi, Charles Han
dc.contributor.authorLee, Tong Ihn
dc.contributor.authorYoung, Richard A
dc.date.accessioned2017-06-20T17:39:19Z
dc.date.available2017-06-20T17:39:19Z
dc.date.issued2017-06-20
dc.date.submitted2016-01
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/1721.1/110068
dc.description.abstractThe non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants. Among the 102 tumour cell genomes we analyse, small insertions are frequently observed in enhancer DNA sequences near known oncogenes. Further study of one insertion, somatically acquired in primary leukaemia tumour genomes, reveals that it nucleates formation of an active enhancer that drives expression of the LMO2 oncogene. The approach described here to identify enhancer-associated small insertion variants provides a foundation for further study of these abnormalities across human cancers.en_US
dc.description.sponsorshipUnited States. National Institutes of Health (HG002668)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (CA109901)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/ncomms14385en_US
dc.rightsCreative Commons Attribution 4.0 International Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNatureen_US
dc.titleSmall genomic insertions form enhancers that misregulate oncogenesen_US
dc.typeArticleen_US
dc.identifier.citationAbraham, Brian J.; Hnisz, Denes; Weintraub, Abraham S.; Kwiatkowski, Nicholas; Li, Charles H.; Li, Zhaodong; Weichert-Leahey, Nina et al. “Small Genomic Insertions Form Enhancers That Misregulate Oncogenes.” Nature Communications 8 (February 2017): 14385 © The Author(s) 2017en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorAbraham, Brian Joseph
dc.contributor.mitauthorWeintraub, Abraham Selby
dc.contributor.mitauthorKwiatkowski, Nick
dc.contributor.mitauthorLi, Charles Han
dc.contributor.mitauthorLee, Tong Ihn
dc.contributor.mitauthorYoung, Richard A
dc.relation.journalNature Communicationsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsAbraham, Brian J.; Hnisz, Denes; Weintraub, Abraham S.; Kwiatkowski, Nicholas; Li, Charles H.; Li, Zhaodong; Weichert-Leahey, Nina; Rahman, Sunniyat; Liu, Yu; Etchin, Julia; Li, Benshang; Shen, Shuhong; Lee, Tong Ihn; Zhang, Jinghui; Look, A. Thomas; Mansour, Marc R.; Young, Richard A.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-0998-9882
dc.identifier.orcidhttps://orcid.org/0000-0001-8091-6112
dc.identifier.orcidhttps://orcid.org/0000-0001-8855-8647
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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